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Cerebral mitochondrial electron transport chain dysfunction in multiple system atrophy and Parkinson's disease.

Foti, SC, Hargreaves, IP, Carrington, S, Kiely, AP, Houlden, H and Holton, JL (2019) Cerebral mitochondrial electron transport chain dysfunction in multiple system atrophy and Parkinson's disease. Scientific Reports, 9 (1). ISSN 2045-2322

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Multiple system atrophy (MSA) is a neurodegenerative disease characterised by glial cytoplasmic inclusions (GCIs), containing α-synuclein. Mutated COQ2, encoding an enzyme essential for co-enzyme Q10 (CoQ10) biosynthesis, has been associated with MSA. CoQ10 is an electron carrier in the mitochondrial electron transport chain (ETC) and antioxidant. It has been shown to be deficient in MSA brain tissue, thus implicating mitochondrial dysfunction in MSA. To investigate mitochondrial dysfunction in MSA further we examined ETC activity in MSA and control brain tissue, compared with Parkinson's disease (PD) where mitochondrial dysfunction is known to be important. Using cerebellar and occipital white matter ETC complex I, II/III and IV activities were measured spectrophotometrically, selected individual components of the ETC were assessed by immunoblotting and cellular complex IV activity was analysed by enzyme histochemistry. We show decreased complex II/III activity with increased complex I and IV activity in MSA cerebellar white matter. This corresponds with the deficit in CoQ10 previously described in MSA and reflects the high regional pathological burden of GCIs. This study highlights mitochondrial dysfunction in MSA pathogenesis, suggests an influence on selective regional vulnerability to disease and points to shared disease mechanisms in α-synucleinopathies.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Nature Research
Related URLs:
Date Deposited: 10 May 2019 09:44
Last Modified: 04 Sep 2021 09:26
DOI or Identification number: 10.1038/s41598-019-42902-7
URI: https://researchonline.ljmu.ac.uk/id/eprint/10659

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